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Anti-Proliferative Role of the Tyrosine Kinase Inhibitors TKI-258 on Oral Squamous Cell Carcinoma In Vitro

Isadora C Silveira1, Anna Cecília D M Carneiro1, Lorraine S Hiss1

  • 1Structural Biology Department, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.

Anti-Cancer Agents in Medicinal Chemistry
|February 14, 2020
PubMed
Abstract

Insights

Tyrosine kinase inhibitor TKI-258 significantly reduced Oral Squamous Cell Carcinoma (OSCC) cell proliferation. Combining TKI-258 with PI3K inhibition further enhanced this anti-proliferative effect, showing promise for OSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Oral Squamous Cell Carcinoma (OSCC) presents high mortality rates, necessitating novel therapeutic strategies.
  • Tyrosine kinase inhibitors (TKIs) are emerging as potential antitumor agents.
  • TKI-258 targets multiple receptors including Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), and Endothelial Growth Factor Receptor (VEGFRs).

Purpose of the Study:

  • To investigate the anti-proliferative effects of TKI-258 on OSCC SCC-4 cells.
  • To evaluate the impact of TKI-258, alone and in combination with PI3K inhibitors, on cancer cell proliferation.

Main Methods:

  • SCC-4 cells were treated with varying concentrations of TKI-258 (1, 5, 10μM) and PI3K inhibitors (LY294002, Wortmannin).
  • Cell proliferation was assessed using Bromodeoxyuridine (BrdU) and KI-67 immunofluorescence assays.
  • Quantitative analysis of proliferative cells was performed, with statistical significance set at p<0.05.

Main Results:

  • TKI-258 demonstrated a dose-dependent reduction in SCC-4 cell proliferation.
  • Inhibition of PI3K pathways led to a significant decrease in the percentage of proliferative cells.
  • Combined treatment with TKI-258 and PI3K inhibitors resulted in a greater reduction in proliferation compared to TKI-258 alone.

Conclusions:

  • TKI-258 exhibits a significant anti-proliferative role in OSCC SCC-4 cells.
  • Targeting multiple pathways (FGFRs, PDGFRs, VEGFRs) with TKI-258 is a viable therapeutic approach for OSCC.
  • The combination of TKI-258 with PI3K inhibition represents a promising strategy for novel OSCC therapeutics.
Keywords:
BrdUKI-67PI3KSCC-4oral squamous cell carcinomatyrosine kinase inhibitors.

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